RECEPTOR-MEDIATED DESENSITIZATION OF HISTAMINE H-1 RECEPTOR-STIMULATED INOSITOL PHOSPHATE PRODUCTION AND CALCIUM MOBILIZATION IN GT1-7 NEURONAL CELLS IS INDEPENDENT OF PROTEIN-KINASE-C

GT1-7 cells, a clonal line derived from specific tumours of gonadotrop in-releasing hormone-secreting neurons from mouse hypothalamus, were u sed as a model system to investigate the cellular mechanisms underlyin g the histamine H-1 receptor-mediated desensitisation. GT1-7 cells con tain H-1 receptors, acute stimulation of which leads to the desensitis ation of histamine-mediated calcium mobilisation and is manifest as a concurrent reduction in both the magnitude of the calcium transient an d of the sustained phase. Acute pretreatment of the cells with the pho rbol ester, phorbol 12-myristate 13-acetate, can also ablate the hista mine-stimulated calcium mobilisation. In addition, acute H-1-receptor stimulation and acute phorbol ester treatment result in the attenuatio n of histamine-mediated inositol phosphate production. Receptor desens itisation resulting from acute stimulation with histamine is not affec ted by inhibiting protein kinase C (PKC) activity with Ro 31-7549 or s taurosporine. In contrast, the desensitisation of H-1-receptor respons es induced by direct activation of protein kinase C is preventable by PKC inhibitors. Thus, these results imply that a PKC-dependent mechani sm and PKC-independent mechanism are involved in the H-1-receptor dese nsitisation cascade in GT1-7 cells and do not support the involvement of PKC in the receptor-mediated desensitisation of H-1 receptor-stimul ated calcium and inositol phosphate responses.